title: Expression of connexin 43 in the human epileptic and drug-resistant cerebral cortex.
abstract: BACKGROUND
  Gap junctions are specialized channels composed of several connexins, membrane proteins that mediate electrical and metabolic coupling between cells. Previous data have suggested that changes in the expression of Cx43, the main astrocytic Cx isoform, may be involved in seizure activity in human epileptic tissue. However, Cx43 has never been examined in focal cortical dysplasia (FCD) and in other human refractory epilepsies.
  
  
  METHODS
  We analyzed Cx43 protein localization and Cx43 mRNA levels in surgical specimens of cortex from a cohort of patients with intractable epilepsy vs control nonepileptic tissue. Samples had neuropathologically defined diagnosis of cryptogenic epilepsy or epilepsy secondary to FCD.
  
  
  RESULTS
  Cx43 immunoreactivity, which labeled punctate elements, did not reveal distinctive features in cryptogenic epilepsy and FCD type IA and IIA. A peculiar pattern of immunolabeling was instead observed in FCD type IIB, in which large aggregates of Cx43-immunopositive puncta were clustered around subsets of balloon cells and astrocytes. Further characterization revealed that these balloon cells do not express markers of precursor cells, such as CD34. Quantitative real-time reverse transcriptase PCR showed elevated levels of Cx43 transcript in a subgroup (25%) of cryptogenic epilepsy specimens compared to control and FCD ones.
  
  
  CONCLUSIONS
  Our study points out that a rearrangement of Cx43-positive elements is part of abnormal tissue organization in FCD type IIB, and that cryptogenic epilepsies include forms with increased Cx43 mRNA expression. The data implicate functional consequences of altered Cx43 expression, and therefore of altered gap junctional coupling, in abnormal network properties of subtypes of human refractory epilepsies.
authors.affiliation: Clinical Epileptology and Experimental Neurophysiology Unit, Fondazione IRCCS, Istituto Neurologico "C. Besta," Via Celoria 11, 20133, Milan, Italy. garbelli.r@istituto-besta.it
authors.forename: R
authors.initials: R
authors.lastname: Garbelli
authors.forename: C
authors.initials: C
authors.lastname: Frassoni
authors.forename: D F
authors.initials: DF
authors.lastname: Condorelli
authors.forename: A
authors.initials: A
authors.lastname: Trovato Salinaro
authors.forename: N
authors.initials: N
authors.lastname: Musso
authors.forename: V
authors.initials: V
authors.lastname: Medici
authors.forename: L
authors.initials: L
authors.lastname: Tassi
authors.forename: M
authors.initials: M
authors.lastname: Bentivoglio
authors.forename: R
authors.initials: R
authors.lastname: Spreafico
mesh_terms: D000293:Adolescent; D000328:Adult; D002540:Cerebral Cortex / Q000378:metabolism*; D002648:Child; D015331:Cohort Studies; D018031:Connexin 43 / Q000235:genetics / Q000378:metabolism*; D004827:Epilepsy / Q000473:pathology*; D005260:Female; D015870:Gene Expression / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D055815:Young Adult
chemical_list: D018031:Connexin 43; C500216:GJA1 protein, human; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger